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Publication : Protoporphyrin IX accumulation disrupts mitochondrial dynamics and function in ABCG2-deficient hepatocytes.

First Author  Lin YH Year  2013
Journal  FEBS Lett Volume  587
Issue  19 Pages  3202-9
PubMed ID  23954234 Mgi Jnum  J:201884
Mgi Id  MGI:5516128 Doi  10.1016/j.febslet.2013.08.011
Citation  Lin YH, et al. (2013) Protoporphyrin IX accumulation disrupts mitochondrial dynamics and function in ABCG2-deficient hepatocytes. FEBS Lett 587(19):3202-9
abstractText  Targeted inhibition of multidrug ABCG2 transporter is believed to improve cancer therapeutics. However, the consequences of ABCG2 inhibition have not been systematically evaluated since ABCG2 is expressed in several organs including the liver. Here, we demonstrate that ABCG2-deficient hepatocytes have increased amounts of fragmental mitochondria accompanied by disruption of mitochondrial dynamics and functions. This disruption was due to ABCG2 knockout elevating intracellular protoporphyrin IX, which led to upregulation of DRP-1-mediated mitochondrial fission. The finding that ABCG2 deficiency can generate dysfunctional mitochondria in hepatocytes raises concerns regarding the systematic use of ABCG2 inhibitor in cancer patients.
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